Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors

Shinnosuke Hosoda; Daisuke Matsuda; Hiroshi Tomoda; Mariko Hashimoto; Hiroshi Aoyama; Yuichi Hashimoto

doi:10.1016/j.bmcl.2009.05.100

Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4228-31. doi: 10.1016/j.bmcl.2009.05.100. Epub 2009 May 29.

Authors

Shinnosuke Hosoda¹, Daisuke Matsuda, Hiroshi Tomoda, Mariko Hashimoto, Hiroshi Aoyama, Yuichi Hashimoto

Affiliation

¹ Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

PMID: 19502059
DOI: 10.1016/j.bmcl.2009.05.100

Abstract

Based on our hypothesis that the 3,3-diphenylpentane (DPP) skeleton is useful as a multi-template for creation of various biologically active compounds and acts as a steroid skeleton substitute, we designed and synthesized novel HMG-CoA reductase inhibitors with a DPP skeleton. Among them, sodium (E,3R,5S)-7-(2-(4-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxy-hept-6-enoate showed potent HMG-CoA reductase-inhibitory activity comparable with that of clinically useful mevastatin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androgens / chemistry
Animals
Chemistry, Pharmaceutical / methods
Drug Design
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemical synthesis*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Inhibitory Concentration 50
Lovastatin / analogs & derivatives
Lovastatin / chemical synthesis
Lovastatin / pharmacology
Models, Chemical
Molecular Structure
Pentanes / chemical synthesis*
Pentanes / pharmacology
Rats
Structure-Activity Relationship

Substances

3,3-diphenylpentane
Androgens
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pentanes
mevastatin
Lovastatin